Gut-brain communication turned on its axis

How the gut communicates with the brain
Image Credit: Copilot AI

The mechanisms by which antidepressants and other emotion-focused medications work could be reconsidered due to an important new breakthrough in the understanding of how the gut communicates with the brain.

New research led by Flinders University has uncovered major developments in understanding how the gut communicates with the brain, which could have a profound impact on the make-up and use of medications such as antidepressants.

“The gut-brain axis consists of complex bidirectional neural communication pathway between the brain and the gut, which links emotional and cognitive centers of the brain,” says Professor Nick Spencer from the College of Medicine and Public Health.

“As part of the gut-brain axis, vagal sensory nerves relay a variety of signals from the gut to the brain that play an important role in mental health and wellbeing.

“The mechanisms by which vagal sensory nerve endings in the gut wall are activated has been a major mystery but remains of great interest to medical science and potential treatments for mental health and wellbeing.”

Human stem cells coaxed to mimic the very early central nervous system

Jianping Fu, Ph.D., Professor of Mechanical Engineering at the University of Michigan and the corresponding author of the paper being published at Nature discusses his team’s work in their lab with Jeyoon Bok, Ph.D. candidate at the Department of Mechanical Engineering.
Photo Credit: Marcin Szczepanski, Michigan Engineering

The first stem cell culture method that produces a full model of the early stages of the human central nervous system has been developed by a team of engineers and biologists at the University of Michigan, the Weizmann Institute of Science, and the University of Pennsylvania.

“Models like this will open doors for fundamental research to understand early development of the human central nervous system and how it could go wrong in different disorders,” said Jianping Fu, U-M professor of mechanical engineering and corresponding author of the study in Nature.

The system is an example of a 3D human organoid—stem cell cultures that reflect key structural and functional properties of human organ systems but are partial or otherwise imperfect copies.

“We try to understand not only the basic biology of human brain development, but also diseases—why we have brain-related diseases, their pathology, and how we can come up with effective strategies to treat them,” said Guo-Li Ming, who along with Hongjun Song, both Perelman Professors of Neuroscience at UPenn and co-authors of the study, developed protocols for growing and guiding the cells and characterized the structural and cellular characteristics of the model.

Study sheds light on how neurotransmitter receptors transport calcium, a process linked with origins of neurological disease

Illustration Credit: Courtesy of McGill University

A new study from a team of McGill University and Vanderbilt University researchers is shedding light on our understanding of the molecular origins of some forms of autism and intellectual disability.

For the first time, researchers were able to successfully capture atomic resolution images of the fast-moving ionotropic glutamate receptor (iGluR) as it transports calcium. iGluRs and their ability to transport calcium are vitally important for many brain functions such as vision or other information coming from sensory organs. Calcium also brings about changes in the signaling capacity of iGluRs and nerve connections which are a key cellular events that lead to our ability to learn new skills and form memories.

iGluRs are also key players in brain development and their dysfunction through genetic mutations has been shown to give rise to some forms of autism and intellectual disability. However, basic questions about how iGluRs trigger biochemical changes in the brain’s physiology by transporting calcium have remained poorly understood.

In the study, the researchers took millions of snapshots of the iGluR protein in the act of transporting calcium, and unexpectedly discovered a temporary pocket that traps calcium on the outside of the protein. With this information at hand, they then used high-resolution electrophysiological recordings to watch the protein in motion as it transported calcium into the nerve cell.

Arterial Connections Improve Treatment Outcomes Following Stroke

Visualization of the blood vessels in the brain of a patient without early venous filling, meaning without excessive reperfusion of the brain area after removal of the blood clot in the blocked artery.
Image Credit: P. Thurner und Z. Kulcsar, USZ

Blood vessels that cross-connect adjacent arterial trees regulate blood flow to the brain in stroke patients. Researchers at the University of Zurich have now shown that these vessels prevent brain hemorrhage following treatment to remove blood clots. They play a crucial role in the recovery of stroke patients.

Ischemic strokes are a major health burden. They occur when a blood vessel that supplies the brain becomes blocked, impairing blood flow to the brain. As a result, brain tissue suffers from a lack of oxygen and nutrients, which causes symptoms such as paralysis, confusion, dizziness, headache, trouble speaking or even death.

Many stroke patients recover poorly despite timely treatment

To treat these symptoms and restore blood flow to the brain, the obstructed vessel needs to be “declogged”, or recanalized. Contemporary treatments to remove the clot include intravenous thrombolysis or mechanical thrombectomy using a catheter. However, even with timely clot removal, many stroke patients only recover poorly.

The research group of Susanne Wegener, professor at the University of Zurich (UZH) and senior leading physician at the Department of Neurology of the University Hospital Zurich (USZ), has now demonstrated that the outcome of stroke treatments depends on the collateral network. Collaterals are blood vessels that cross-connect adjacent arterial trees, providing potential detour networks in case of a vascular blockage. “These vascular bridges maintain cerebral autoregulation and allow for a slower, gradual reperfusion, which results in smaller infarcts,” says Wegener.

How bats distinguish different sounds

Seba's short-tailed bat (Carollia perspicillata) filters out important signals from ambient sound and distinguishes between echolocation and communication calls.
Photo Credit: Julio Hechavarría, Goethe University Frankfurt

Bats live in a world of sounds. They use vocalizations both to communicate with their conspecifics and for navigation. For the latter, they emit sounds in the ultrasonic range, which echo and enable them to create an “image" of their surroundings. Neuroscientists at Goethe University Frankfurt have now discovered how Seba's short-tailed bat, a species native to South America, manages to filter out important signals from ambient sound and especially to distinguish between echolocation and communication calls. 

Seba's short-tailed bat (Carollia perspicillata) lives in the subtropical and tropical forests of Central and South America, where it mostly feeds on pepper fruit. The animals spend their days in groups of 10 to 100 individuals in hollow trunks and rocky caverns, and at night they go foraging together. They communicate using sounds that create distinct ambient noise in the colony – like the babble of voices at a lively party. At the same time, the bats also use vocalizations to navigate their surroundings: a phenomenon known as echolocation, for which they emit ultrasonic sounds that reflect off solid surfaces. The animals then assemble these echoes into an “image" of their surroundings. 

Newly discovered brain cells play a key role in right and left turns

Researchers have discovered a new group of neurons in the brainstem which control the right-left circuit.
Graphic Credit: Canva. Courtesy of University of Copenhagen

Researchers have discovered a network of neurons in the brain of mice that help them make right and left turns. In the future, the discovery may be used in treatment for Parkinson’s disease.

Have you ever wondered what happens in the brain when we move to the right or left? Most people don’t; they just do it without thinking about it. But this simple movement is actually controlled by a complex process. 

In a new study, researchers have discovered the missing piece in the complex nerve-network needed for left-right turns. The discovery was made by a research team consisting of Assistant Professor Jared Cregg, Professor Ole Kiehn, and their colleagues from the Department of Neuroscience at the University of Copenhagen. 

In 2020, Ole Kiehn, Jared Creeg and their colleagues identified the ‘brain’s steering wheel’ – a network of neurons in the lower part of the brainstem that commands right- and left- movements when walking. At the time, though, it was not clear to them how this right-left circuit is controlled by other parts of the brain, such as the basal ganglia. 

“We have now discovered a new group of neurons in the brainstem which receives information directly from the basal ganglia and controls the right-left circuit,” Ole Kiehn explains. 

Eventually, this discovery may be able to help people suffering from Parkinson’s disease. The study has been published in the scientific journal Nature Neuroscience.  

How Does the Brain Make Decisions?

Image Credit: Generated by HM News with AI in Adobe Firefly

Scientists have gained new insights into how neurons in the brain communicate during a decision, and how the connections between neurons may help reinforce a choice.

The study — conducted in mice and led by neuroscientists at Harvard Medical School — is the first to combine structural, functional, and behavioral analyses to explore how neuron-to-neuron connections support decision-making.

“How the brain is organized to help make decisions is a big, fundamental question, and the neural circuitry — how neurons are connected to one another — in brain areas that are important for decision-making isn’t well understood,” said Wei-Chung Allen Lee, associate professor of neurobiology in the Blavatnik Institute at HMS and professor of neurology at Boston Children’s Hospital. Lee is co-senior author on the paper with Christopher Harvey, professor of neurobiology at HMS, and Stefano Panzeri, professor at University Medical Center Hamburg-Eppendorf.

In the research, mice were tasked with choosing which way to go in a maze to find a reward. The researchers found that a mouse’s decision to go left or right activated sequential groups of neurons, culminating in the suppression of neurons linked to the opposite choice.

These specific connections between groups of neurons may help sculpt decisions by shutting down neural pathways for alternative options, Lee said.

NIH study offers new clues into the causes of post-infectious ME/CFS

In-depth study finds brain, immune, and metabolic abnormalities linked to debilitating chronic disease.
Image Credit: John A Beal
(CC BY 4.0 DEED)

In a detailed clinical study, researchers at the National Institutes of Health have found differences in the brains and immune systems of people with post-infectious myalgic encephalomyelitis/chronic fatigue syndrome (PI-ME/CFS). They also found distinct differences between men and women with the disease. The findings were published in Nature Communications.

“People with ME/CFS have very real and disabling symptoms, but uncovering their biological basis has been extremely difficult,” said Walter Koroshetz, M.D., director of NIH’s National Institute of Neurological Disorders and Stroke (NINDS). “This in-depth study of a small group of people found a number of factors that likely contribute to their ME/CFS. Now researchers can test whether these findings apply to a larger patient group and move towards identifying treatments that target core drivers of the disease.”

A team of multidisciplinary researchers discovered how feelings of fatigue are processed in the brains of people with ME/CFS. Results from functional magnetic resonance imaging (fMRI) brain scans showed that people with ME/CFS had lower activity in a brain region called the temporal-parietal junction (TPJ), which may cause fatigue by disrupting the way the brain decides how to exert effort.

They also analyzed spinal fluid collected from participants and found abnormally low levels of catecholamines and other molecules that help regulate the nervous system in people with ME/CFS compared to healthy controls. Reduced levels of certain catecholamines were associated with worse motor performance, effort-related behaviors, and cognitive symptoms. These findings, for the first time, suggest a link between specific abnormalities or imbalances in the brain and ME/CFS.

Sleep improves ability to recall complex events

Sleep is important for reinforcing complex associations, the basis for completing memories of entire events
Photo Credit: Shane

Researchers have known for some time that sleep consolidates our memories of facts and episodic events. However, the research to date has concentrated mainly on simple associations – that is to say, connections between elements, such as we make when learning new vocabulary. “But in real life, events are generally made up of numerous components – for example, a place, people, and objects – which are linked together in the brain,” explains Dr. Nicolas Lutz from LMU’s Institute of Medical Psychology. These associations can vary in strength and some elements might be connected with each other only indirectly. “Thanks to the neural connections that underlie these associations, a single cue word is often all it takes for somebody to recall not only individual aspects of an event but multiple aspects at once.” This process, which is known as pattern completion, is a fundamental feature of episodic memory. Lutz is lead author of a study recently published in the journal Proceedings of the National Academy of Sciences (PNAS), which investigated the effect of sleep on memory of such complex events.

Where Neural Stem Cells Feel at Home

In the laboratory, the Bochum researchers are investigating which environment offers neural stem cells the best chances of survival.
Photo Credit: © RUB, Marquard

Injuries in the central nervous system heal poorly because cavities scar. Researchers hope to remedy this problem by filling the cavities in such a way that stem cells feel comfortable in them.

Researchers from Bochum and Dortmund have created an artificial cell environment that could promote the regeneration of nerves. Usually, injuries to the brain or spinal cord don’t heal easily due to the formation of fluid-filled cavities and scars that prevent tissue regeneration. One starting point for medical research is therefore to fill the cavities with a substance that offers neural stem cells optimal conditions for proliferation and differentiation. The team from Ruhr University Bochum and TU Dortmund University, both in Germany, showed that positively charged hydrogels can promote the survival and growth of stem cells.

Dr. Kristin Glotzbach and Professor Andreas Faissner from the Department of Cell Morphology and Molecular Neurobiology in Bochum cooperated with Professor Ralf Weberskirch and Dr. Nils Stamm from the Faculty of Chemistry and Chemical Biology at TU Dortmund University. The team describes the findings in the American Chemical Society Journal Biomaterials Science and Engineering.

Oregon State study sheds light on links between cognitive and motor skill development in children with autism

Image Credit: Aedrian

A recent study by Oregon State University researchers highlighted the ways motor skills and cognitive skills develop in connection with each other in young children with autism, and found an opportunity for behavioral and physical therapists to work together to improve care.

“We know they’re highly linked, but we often talk about them in different domains,” said study co-author Megan MacDonald, head of the School of Exercise, Sport, and Health Science in OSU’s College of Health. “When we look at wraparound services and talk about academic, social, physical and cognitive services, there’s so much we could do together.”

When assessing, diagnosing and providing services for young children with autism, providers are often siloed from each other, MacDonald said. Occupational and physical therapists focus on fine and gross motor skills, while behavioral therapists focus on emotional regulation and executive function.

But in many situations, the two sides depend on each other, she said. Fine motor skills are closely linked to cognition, such as the combination of moves kids must remember and perform in the correct order to write their name. The gross motor skills used in a playground game of kickball work in tandem with the social and emotional skills used to interact with other students and work as a team.

The brain is 'programmed' for learning from people we like

Image Credit: Gemini Advance AI

Our brains are "programmed" to learn more from people we like – and less from those we dislike. This has been shown by researchers in cognitive neuroscience in a series of experiments.

Memory serves a vital function, enabling us to learn from new experiences and update existing knowledge. We learn both from individual experiences and from connecting them to draw new conclusions about the world. This way, we can make inferences about things that we don't necessarily have direct experience of. This is called memory integration and makes learning quick and flexible.

Inês Bramão, associate professor of psychology at Lund University, provides an example of memory integration: Say you're walking in a park. You see a man with a dog. A few hours later, you see the dog in the city with a woman. Your brain quickly makes the connection that the man and woman are a couple even though you have never seen them together. 

“Making such inferences is adaptive and helpful. But of course, there's a risk that our brain draws incorrect conclusions or remembers selectively”, says Inês Bramão.

New Algorithm Disentangles Intrinsic Brain Patterns from Sensory Inputs

Image Credit: Omid Sani, Using Generative Ai

Maryam Shanechi, Dean’s Professor of Electrical and Computer Engineering and founding director of the USC Center for Neurotechnology, and her team have developed a new machine learning method that reveals surprisingly consistent intrinsic brain patterns across different subjects by disentangling these patterns from the effect of visual inputs.

The work has been published in the Proceedings of the National Academy of Sciences (PNAS).

When performing various everyday movement behaviors, such as reaching for a book, our brain has to take in information, often in the form of visual input — for example, seeing where the book is. Our brain then has to process this information internally to coordinate the activity of our muscles and perform the movement. But how do millions of neurons in our brain perform such a task? Answering this question requires studying the neurons’ collective activity patterns, but doing so while disentangling the effect of input from the neurons’ intrinsic (aka internal) processes, whether movement-relevant or not.

That’s what Shanechi, her PhD student Parsa Vahidi, and a research associate in her lab, Omid Sani, did by developing a new machine-learning method that models neural activity while considering both movement behavior and sensory input.

Desert Ants: The Magnetic Field Calibrates the Navigation System

The desert ant Cataglyphis nodus at its nest entrance - an inconspicuous hole in the ground that cannot be seen from the ant's perspective. To find its way back there, the ant uses the earth's magnetic field during its learning walks.
Photo Credit: Robin Grob

Desert ants find their way during an early learning phase with the help of the Earth's magnetic field. The associated learning process leaves clear traces in their nervous system. This is shown in a new study by a Würzburg research team.

They are only a few centimeters tall and their brains have a comparatively simple structure with less than one million neurons. Nevertheless, desert ants of the Cataglyphis genus possess abilities that distinguish them from many other creatures: The animals are able to orient themselves to the Earth's magnetic field.

Visible Changes in the Nervous System

A research team from Julius-Maximilians-Universität Würzburg (JMU) discovered this a few years ago. However, it was previously unknown where in the ants' brains the magnetic information is processed. This has now changed: In a new study published in the journal PNAS - Proceedings of the National Academy of Sciences, the team shows that information about the Earth's magnetic field is primarily processed in the ants' internal compass, the so-called central complex, and in the mushroom bodies, the animals' learning and memory centers.

Researchers identify brain hub with key role in learned response to direct and indirect threats

Diagram of mouse prefrontal cortex showing neural projections to the midbrain (purple) and the amygdala (green), pathways involved in learning about threat.
Image Credit: National Institute on Alcohol Abuse and Alcoholism

NIH-supported study in mice could inform treatments of trauma- and stress-related psychiatric conditions.

Scientists have identified an area within the brain’s frontal cortex that may coordinate an animal’s response to potentially traumatic situations. Understanding where and how neural circuits involving the frontal cortex regulate such functions, and how such circuits could malfunction, may provide insight about their role in trauma-related and stress-related psychiatric disorders in people. The study, led by scientists at the National Institute on Alcohol Abuse and Alcoholism (NIAAA), a part of the National Institutes of Health, was published in Nature.

“Experiencing traumatic events is often at the root of trauma-related and stress-related psychiatric conditions, including alcohol use disorder (AUD),” said the study’s senior author, Andrew Holmes, Ph.D., senior investigator in NIAAA’s Laboratory of Behavioral and Genomic Neuroscience. “Additionally, witnessing others experience traumatic events can also contribute to these disorders.”

Risk of young-onset dementia could be reduced through targeting health and lifestyle factors

Researchers have identified a wide range of risk factors for young-onset dementia. The findings challenge the notion that genetics are the sole cause of the condition, laying the groundwork for new prevention strategies.

The largescale study identified 15 risk factors, which are similar to those for late-onset dementia. For the first time, they indicate that it may be possible to reduce the risk of young-onset dementia by targeting health and lifestyle factors.

Relatively little research has been done on young-onset dementia, though globally there are around 370,000 new cases of young-onset dementia each year.

Published in JAMA Neurology, the new research by the University of Exeter and Maastricht University followed more than 350,000 participants younger than 65 across the United Kingdom from the UK Biobank study. The team evaluated a broad array of risk factors ranging from genetic predispositions to lifestyle and environmental influences. The study revealed that lower formal education, lower socioeconomic status, genetic variation, lifestyle factors such as alcohol use disorder and social isolation, and health issues including vitamin D deficiency, depression, stroke, hearing impairment and heart disease significantly elevate risk of young-onset dementia

Light color is less important for the internal clock than originally thought

To what extent does the color of light influence our internal clock and sleep? The results of a study conducted in Basel shed light on this.
Photo Credit: Josh Hild

Light in the evening is thought to be bad for sleep. However, does the color of the light play a role? Researchers from the University of Basel and the Technical University of Munich (TUM) compared the influence of different light colors on the human body. The researchers’ findings contradict the results of a previous study in mice.

Vision is a complex process. The visual perception of the environment is created by a combination of different wavelengths of light, which are decoded as colors and brightness in the brain. Photoreceptors in the retina first convert the light into electrical impulses: with sufficient light, the cones enable sharp, detailed, and colored vision. Rods only contribute to vision in low light conditions allowing for different shades of grey to be distinguished but leaving vision much less precise. The electrical nerve impulses are finally transmitted to ganglion cells in the retina and then via the optic nerve to the visual cortex in the brain. This region of the brain processes the neural activity into a colored image.

A Trillion Scents. One Nose.

The genome inside an olfactory cell’s nucleus is shown as a tangle of color-marked chromosomes with genomic locations of olfactory receptor genes revealed on the right
Illustration Credit: Lomvardas lab, Columbia's Zuckerman Institute

The mammalian nose is a work of evolutionary art. Its millions of nerve cells, each tailored with just one of thousands of specific odor-chemical receptors encoded in the genome, can collectively distinguish a trillion distinct scents. Those sensations, in turn, inform many behaviors, from assessing food options to discerning friends from foes to sparking memories. 

Today, in the journal Nature, a research team led by scientists at Columbia’s Zuckerman Institute describes a previously undetected mechanism in mice—starring the genetic molecule RNA—that could explain how each sensory cell, or neuron, in mammalian noses becomes tailored to detect a specific odor chemical. 

For example, there are sensory neurons in our noses that bear receptors uniquely tuned to detect ethyl vanillin, the main odorant in vanilla, and other cells with receptors for limonene, lemon’s signature odorant.

Enlarged Spaces in Infant Brains Linked to Higher Risk of Autism, Sleep Problems

Dea Garic, PhD, and Mark Shen, PhD, both in the UNC School of Medicine’s Department of Psychiatry, have found that enlarged perivascular spaces in the brains of babies, caused by an accumulation of excess cerebrospinal fluid, have a 2.2 times greater chance of developing autism later in life.
Photo Credit: Courtesy of University of North Carolina at Chapel Hill

Throughout the day and night, cerebrospinal fluid (CSF) pulses through small fluid-filled channels surrounding blood vessels in the brain, called perivascular spaces, to flush out neuroinflammation and other neurological waste. A disruption to this vital process can lead to neurological dysfunction, cognitive decline, or developmental delays.

For the first time, researchers Dea Garic, PhD, and Mark Shen, PhD, both at the UNC School of Medicine’s Department of Psychiatry, discovered that infants with abnormally enlarged perivascular spaces have a 2.2 times greater chance of developing autism compared to infants with the same genetic risk. Their research also indicated that enlarged perivascular spaces in infancy are associated with sleep problems seven to 10 years after diagnosis.

“These results suggest that perivascular spaces could serve as an early marker for autism,” said Garic, assistant professor of psychiatry and a member of the Carolina Institute for Developmental Disabilities (CIDD).

The researchers studied infants at increased likelihood for developing autism, because they had an older sibling with autism. They followed these infants from 6-24 months of age, before the age of autism diagnosis. Their study, published in JAMA Network Open, found that thirty percent of infants who later developed autism had enlarged perivascular spaces by 12 months. By 24 months of age, nearly half of the infants diagnosed with autism had enlarged perivascular spaces.

When the Cellular Waste Collector Doesn’t Show Up

Verian Bader and Konstanze Winklhofer (right) are on the trail of the development of neurodegenerative diseases.
Photo Credit: © RUB, Marquard

Researchers have identified a mechanism that promotes the breakdown of harmful protein deposits. If it malfunctions, it can lead to Parkinson’s disease.

NEMO, a protein that is primarily associated with signaling processes in the immune system, prevents the deposition of protein aggregates that occur in Parkinson’s disease. For this purpose, it binds to certain protein chains that serve as markers for cellular waste removal, thus promoting the degradation of the harmful aggregates. A research team headed by Professor Konstanze Winklhofer from Ruhr University Bochum, Germany, has shed light on how this mechanism works. The team published their findings in the journal Nature Communications on December 19, 2023. In follow-up studies, the team is investigating ways to harness the findings for therapeutic strategies.

Looking for targeted therapeutic approaches

Neurodegenerative diseases, such as Parkinson’s or Alzheimer’s disease, are associated with the deposition of protein aggregates in the brain. These aggregates accumulate when the cellular waste removal system is defective or overloaded. In Parkinson’s disease, aggregates consisting primarily of the protein ⍺-synuclein are found in certain regions of the brain. “The fact that such aggregates occur, which are referred to as Lewy bodies, is a key feature of Parkinson’s disease,” explains Konstanze Winklhofer.

The misfolding and aggregation of ⍺-synuclein is of crucial importance for processes that lead to the loss of function and death of neuronal cells and contribute to the progression of the disease. Researchers from various disciplines around the world are therefore aiming to decipher these processes at a cellular and molecular level, in order to develop targeted therapeutic approaches.